Empathy, or the ability to detect and respond to the emotions of others, is a fundamental component of normal social communication and is necessary for the maintenance of social relationships. Many social cognitive disorders, including autism spectrum disorder, schizophrenia, and psychopathy, are characterized by empathy deficits, which impair normal social interaction and decrease quality of life. Nonetheless, the biological mechanisms that underlie empathy are poorly understood, and no medical interventions exist for the treatment of these deficits. Before such medical therapies can be developed, the significant gap in our knowledge about the biology of empathy must be addressed. A variety of recent studies have shown that many animals also have the capacity to detect and respond to the emotions of other animals. Therefore, this gap in knowledge can and should be addressed through the use of appropriate animal models that display empathy-based behaviors analogous to human behaviors. One common empathy-based response to the distress of others in humans is to provide consolation. Social response to distress in others is now known to be present in a small number of animal species, making it an ideal candidate behavior for learning more about the biology of empathy. Our laboratory has demonstrated for the first time that a laboratory rodent, the prairie vole, displays social response to distress under experimental conditions, that this behavior is empathy-based, and that the behavior is abolished through administration of an oxytocin (OT) receptor antagonist directly into the brain. Our lab is therefore uniquely positioned to discover the neurobiological basis of social response to distress in a way that is not possible in any other existing model. We propose to use social response to distress in the prairie vole as a model for learning about the neurobiology of empathy. In pursuit of this knowledge, we propose the following specific experiments. In Aim 1, we propose to locate one or more of the specific brain regions where OT receptor antagonist acts to prevent consolation. We will do so using site-specific infusions of the antagonist in combination with the social distress test developed in our pilot studies. In Aim 2, we will expand on this neural circuit by locating the source of OT release into the region of interest. We will do so using a triple-labeling technique to locate neurons that contain OT, project to the region of interest, and are active during social response to distress. In Aim 3, we propose to determine how natural variations in OT receptor density during development impact consolation. To determine this, we will experimentally manipulate the density of OT receptors in juvenile prairie voles using viral vector techniques developed in our laboratory, and measure the impact of these manipulations at adulthood on social response to distress. The results of these experiments will begin to bridge the gap in our knowledge of empathy by providing the first evidence of a behavioral circuit for social response to distress in the prairie vole. The proposed experiments will expand our knowledge of social cognition and the neurobiology of social response to distress. In addition, these findings may inform future studies into the clinical treatment of empathy deficits.